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| Clinical data | |
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| Other names | N-(3-Diethylamino-3-oxopropyl)-NMT;N-DEAOP-NMT;N-(2-Diethylcarbamoylethyl)-N-methyltryptamine;N-DECE-NMT; NMT-N-(CH2-CH2-CONEt2) |
| Drug class | Simplified/partial LSD analogue |
| Chemical and physical data | |
| Formula | C18H27N3O |
| Molar mass | 301.434 g·mol−1 |
| 3D model (JSmol) | |
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N-(3-Diethylamino-3-oxopropyl)-N-methyltryptamine (N-DEAOP-NMT) is atryptaminederivative and a "partial" or simplifiedergoline which is closely related to the highlypotentserotonergic psychedeliclysergic acid diethylamide (LSD).[1][2][3][4] It is theanalogue of LSD in which two of LSD'scarbonatoms in the ergolinering, those at positions 9 and 10, have been removed.[1][2][3][4] This in turn renders theN-DEAOP-NMT molecule flexible and makes it anon-rigid tryptamine rather than an ergoline.[1][2][3][4] The compound ispharmacologically active, as are a number of its analogues and derivatives, with activities of the compounds includingserotonin5-HT2A receptoragonism and LSD- orhallucinogen-like effects.[1][2][3][4]
N-DEAOP-NMT has been found to produce quantifiableoxytocic effects in animals.[1][4] However, in contrast to otherlysergamides such aslysergic acid andergonovine (ergometrine),N-DEAOP-NMT was said to not possess significant oxytocic activity relative to clinically used oxytocic drugs, and hence to have little such activity.[1][4] On the other hand, it was noted to possess 10-fold greater oxytocic activity than that ofN-(3-diethylamino-3-oxopropyl)-N-methylphenethylamine (N-DEAOP-NMPEA), aphenethylamine-based simplified and non-rigid LSD analogue that was also evaluated in the study.[4] The oxytocic effects of ergolines like ergonovine andmethylergonovine (methylergometrine) are thought to most likely be mediated byagonism ofserotonin5-HT2 receptors inuterinesmooth muscletissue.[5][6] Relatedly, activation of serotonin5-HT2A receptors in thebrain is also themechanism of action underlying thehallucinogenic effects ofLSD and otherserotonergic psychedelics.[7][8][9]
TheN-ethyl variant ofN-DEAOP-NMT, as opposed toN-DEAOP-NMT itself (which is theN-methyl form), isN-(3-diethylamino-3-oxopropyl)-N-ethyltryptamine (N-DEAOP-NET), and has been described.[1][3] This compound is a simplified and non-rigid analogue ofETH-LAD rather than of LSD (which is also known as "METH-LAD").[1][3] In contrast toN-DEAOP-NMT,N-DEAOP-NET has been evaluated specifically for LSD- orhallucinogen-like effects in animals.[1][3] LSD produced a typical behavioral and physiological syndrome at an effective-to-fatal dose range of 0.1–5.0 mg/kg in rats, whereas the range forN-DEAOP-NET was 1.0–10.0 mg/kg.[1][3] The effects ofN-DEAOP-NET were qualitatively similar to those of LSD, and included strongmydriasis,hyperreflexia,tremors,hypothermia,hyperactivity,skinhyperemia,stereotypy,fearful reactions, anddisorientation, among others.[1][3] Based on the preceding findings, it has been concluded thatN-DEAOP-NET shows LSD-like effects and hence may produce psychedelic effects in humans but is about 10 times lesspotent than LSD at least in rodents.[1][3] Various otheranalogues were also assessed and described.[3]
The 5-methoxy analogue ofN-DEAOP-NMT,N-(3-diethylamino-3-oxopropyl)-N-methyl-5-methoxytryptamine (5-MeO-N-DEAOP-NMT), also known asN-(2-diethylcarbamoylethyl)-N-methyl-5-methoxytryptamine (5-MeO-N-DECE-NMT), has been described.[2] Itsaffinities (Ki) forserotonin receptors were 21 nM for theserotonin5-HT1A receptor, 697 nM for the serotonin5-HT2A receptor, and 1,184 nM for the serotonin5-HT2C receptor.[2] For comparison, the serotonergic psychedelicdimethyltryptamine (DMT) had affinities for these receptors of 38 nM, 1,093 nM, and 211 nM, respectively, while the psychedelic5-MeO-DMT had affinities of 4.2 nM, 558 nM, and 187 nM, respectively.[2] 5-MeO-N-DEAOP-NMT was apartial agonist of the serotonin 5-HT2A receptor, with anEC50Tooltip half-maximal effective concentration of 2,338 nM and anEmaxTooltip maximal efficacy of 16–40%, whereas DMT was a partial agonist with anEC50 of 2,239 nM and anEmax of 16–41% while 5-MeO-DMT was a partial tofull agonist with anEC50 of 741 nM and anEmax of 57–98%.[2] Hence, 5-MeO-N-DEAOP-NMT showed fairly similar affinities for serotonin receptors andactivational potencies andefficacies at the serotonin 5-HT2A receptor compared to the well-known DMT.[2]N-DEAOP-NMT was also included in the study, but its values were not reported.[2]
5-MeO-N-DEAOP-NET, orN-(3-diethylamino-3-oxopropyl)-N-ethyl-5-methoxytryptamine, the 5-methoxy analogue ofN-DEAOP-NET, was also notably evaluated in the previously discussed animal study of LSD-like effects withN-DEAOP-NE and other analogues, but it was not as potent asN-DEAOP-NET and its dose range was not reported.[3]
Other simplified non-rigid LSD analogues, likeCT-5252 andNDTDI among others, have additionally beensynthesized andassayed.[1][2][3][4][10][11] NDTDI is atricyclic analogue of LSD andN-DEAOP-NMT in which only the carbon atom at position 9 of theergolinering system has been removed, as opposed to removal of both carbons at positions 9 and 10 as in the case ofN-DEAOP-NMT.[12] It has been encountered as an LSD-relateddesigner drug andmade illegal in parts ofEurope.[13][14]
N-DEAOP-NMT was first described in thescientific literature by 1952.[1][4] This followed thesynthesis of LSD by chemistAlbert Hofmann in 1938 and the discovery of LSD's psychedelic effects by Hofmann in 1943.[15]N-DEAOP-NMT and other simplified non-rigid LSD analogues were notably reviewed and discussed by psychedelic chemistDavid E. Nichols in hisPh.D.thesis on LSDanalogues and other psychedelics in 1973.[1]N-DEAOP-NMT'sderivativesN-DEAOP-NET and 5-MeO-N-DEAOP-NET, as well as LSD-like effects of these compounds, were first described in the literature by 1971,[1][3] while 5-MeO-N-DEAOP-NMT and itsserotonin receptor interactions were first described by 2005.[2]
Sklar, et al. (53) found the diethylacrylamide adduct 20 to be approximately 1/10 as active as LSD in mice, although Norris and Blicke (54) reported 21 to have little oxytocic activity. [...] 20 = R = C2H5. 21 = R = CH3 [...] Julia, Igolen and Kolb (50) have prepared 16 and 17 as analogs of lysergic acid but no biological activities have been reported. [...] 50. M. Julia, J. Igolen, and A. Kolb, C. R. Acad. Sci., Paris, Ser. C, 273, 1776 (1971). [...] 53. S. Sklar, K. A. Nieforth, and M. Malone, J. Pharm. Sci., 60, 304 (1971). 54. P. E. Norris and F. F. Blicke, J. Amer. Pharm. Ass. (Scientific ed.), XLI, 637 (1952).
Binding Data for the 5-HT1A receptor [...] Introduction of a carbonyl functionality into the substituent had a detrimental effect on affinity for all tested compounds if compared to the methyl substituent as well as compared to straight alkyl groups of comparable length. [...] Binding affinities of straight chain alkyl compounds at the 5-HT2A receptor [...] As seen for the 5-HT1A receptor, adding carbonyl functionalities to the side chain had strongly detrimental effects on binding affinity. Especially the more hydrophilic CH2-CONH2 substituted compounds 231 and 232 showed negligible binding affinity. Only the longer and more lipophilic (CH2-CH2-CONEt2)-5-MeO-DMT (302) had similar affinity to 5-MeO-NMT (208) and 5-MeO-DMT (15). [...] N-(Carbamoylmethyl)-N-methyltryptamine hydrogen oxalate (2-{[2-(Indol-3-yl)-ethyl]-methylamino}-acetamide hydrogen oxalate) (231) [...] N-(Carbamoylmethyl)-N-methyl-5-methoxytryptamine hydrogen oxalate (2-{[2-(5-Methoxyindol-3-yl)-ethyl]-methylamino}-acetamide hydrogen oxalate) (232) [...] N-(2-Diethylcarbamoylethyl)-N-methyltryptamine hydrogen oxalate (N,N-Diethyl-3-{[2-(indol-3-yl)-ethyl]-methylamino}-propionamide hydrogen oxalate) (301) N-(2-Diethylcarbamoylethyl)-N-methyltryptamine hydrogen oxalate (C18H27N3O⋅C2H2O4, 391.46 g/mol) was obtained as a non-crystallizing oily precipitate from 115.2 mg 3-bromo-N,N-diethylpropionamide (183, 208.1 g/mol, 100%, 553.6 µmol) and 85.3 mg N-methyltryptamine (211, 174.24 g/mol, 489.5 µmol) by general procedure E. N-(2-Diethylcarbamoylethyl)-N-methyl-5-methoxytryptamine hydrogen oxalate (N,N-Diethyl-3-{[2-(5-methoxyindol-3-yl)-ethyl]-methylamino}-propionamide hydrogen oxalate) (302) [...]
Fourteen derivatives of N-ethyltryptamine, structurally related to [...] lysergic acid, were synthesized. These compounds [...] were screened for gross pharmacologic activity in unanesthetized rats. [...] LSD-like activity was found in those compounds most closely related to lysergic acid. [...] Fourteen amides and esters of N-ethyl-N-(3-indolylethyl)-ω-aminoalkyl carboxylic acid were synthesized. [...] Psychotomimetic activity would be anticipated in those compounds that had a two-carbon chain separating the tryptamine and carbonyl function as in lysergic acid diethylamide. [...] The characteristic symptomatology produced by d-lysergic acid diethylamide tartrate (0.1-5.0 mg./kg.) is manifested as a rapid onset of profound mydriasis, pilomotor erection, and hypothermia associated with spontaneous statue positions and stereotypy at doses that do not affect the animal's motor performance significantly. At doses of 1.0-5.0 mg./kg., hyperactivity, hyperreflexia, and tremors are apparent as well as fearful-aggressive reaction patterns to body grasp and head tap challenges. Death following a dosage of 5.0 mg./kg. occurs within 30-45 min. and is associated with cardiac irregularities and general rigidity of musculature, [...] the diethylamino derivatives appeared to possess some qualitatively similar lysergic acid-like activity, with Compound XVI [(N-DEAOP-NET)] being the most potent, [...] Compound XVI, in the equivocally effective-to-lethal dosage range of 1.0-10.0 mg./kg., produced dose-response patterns of strong mydriasis, hyperreflexia, tremors, hypothermia, increased motor activity, hyperemia of skin, and evidences for stereotypy and disorientation. Fearful reaction patterns to the head tap and body grasp challenges were observed uniformly. [...] Each amide showed various degrees of LSD-like activity. The molecule derived directly from the disjuncture of LSD, that is, the diethylamide of the compound where the alkyl chain possesses two carbons, was quantitatively the most potent, showing the desired activity at levels of 1.0-10.0 mg./kg. As the alkyl chain was lengthened, potency decreased. The dimethyl amides were active but to a lesser degree.
Six esters and amides of derivatives of β-alanine which are related to lysergic acid have been prepared and tested for oxytocic activity. None of these products possess a significant oxytocic activity. [...] The purpose of this investigation was to synthesize amides and also esters of compounds (II–V) which represent fragments of the lysergic acid molecule in the hope that some of these products might possess oxytocic activity. Various modified fragments of the lysergic acid molecule have been synthesized previously; it was claimed that some of the compounds are active oxytocics (1—7). [...] Pharmacologic data indicated that none of the esters or amides of compounds II—V which were prepared possess a significant oxytocic action when compared to the clinically used oxytocics. However, the diethylamide of N-methyl-N-[β′-(3-indolyl)-ethyl]-β-alanine (IIIc) appeared to have an oxytocic activity approximately ten times stronger than that of the diethylamide of N-methyl-N-(β′-phenethyl)-β-alanine (IIc).
Ergonovine is a selective and moderately potent tryptaminergic receptor antagonist in various smooth muscles, being only a partially agonistic or antagonistic at tryptaminergic receptors in the central nervous system. In blood vessels the alkaloid is only weakly antagonistic of dopaminergic receptors and partitally agonistic of α-adrenergic receptors. The most pronounced effect of ergonovine is one of direct stimulation of the uterine smooth musculature, resulting in increased muscular tone and an enhancement of the rate and force of rhythmical contractions. This stimulant effect seems to be most closely associated with agonist or partial agonist effects at 5-HT2 receptors. [...] LSD and related hallucinogens are known to interact with brain 5-HT receptors to produce agonist or partial antagonist effects on serotonin activity.
{{cite journal}}: CS1 maint: DOI inactive as of March 2025 (link)Methylergonovine is a serotonergic receptor agonist in the smooth muscle. It is also a weak antagonist of dopaminergic receptors and partial agonist of α-adrenergic receptors.22 Methylergonovine causes uterine contractions and relaxation at low doses, but causes sustained contractions and increased basal tone at high doses.24 The mechanism of action for uterine contraction is not well defined. Uterine contraction is likely produced by methylergonovine agonist effects on the 5-HT2 receptor found in uterine smooth muscle.22 Alternatively, methylergonovine could cause uterine contraction through direct stimulation of the α-adrenergic receptors in the uterus, which has been postulated to lead to calcium mobilization.25
Time and again I hear or read that LSD was an accidental discovery, that LSD was discovered by chance. This is only partly true. LSD was already 5 years old when chance came into play. I had prepared this compound in 1938 in the course of planned research, but it was only in 1943 that I discovered, by chance, its extra- ordinary psychical effects. I had planned to prepare an analeptic, a circulatory stimulant, but then found a psychical stimulant of unprecedented potency. The English vocabulary has a term for such discoveries — 'serendipity' — meaning a kind of planned accident, or planned chance.